Regulation of sterol carrier protein gene expression by  the Forkhead transcription factor FOXO3a

doi:10.1194/jlr.M300111-JLR200

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A more recent version of this article appeared on January 1, 2004

Papers In Press, published online ahead of print October 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300111-JLR200

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Submitted on March 11, 2003
Revised on August 18, 2003
Accepted on October 7, 2003

Regulation of sterol carrier protein gene expression by the Forkhead transcription factor FOXO3a

Tobias B. Dansen, Geert J. P. L. Kops, Simone Denis, Nannette Jelluma, Ronald J. A. Wanders, Johannes L. Bos, Boudewijn M. T. Burgering, and Karel W. A. Wirtz

Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115

Corresponding Author: tdansen{at}cc.ucsf.edu

The SCP gene encodes two proteins, Sterol Carrier Protein X (SCPx) and Sterol Carrier Protein 2 (SCP2), that are independently regulated by separate promoters. SCPx has been shown to be the thiolase involved in the breakdown of branched chain fatty acids and in the biosyntheis of bile acids. The in vivo function of SCP2 however remains to be established. The transcriptional regulation of SCPx and SCP2 is unclear but their promoter regions contain several putative regulatory domains. We show here that both SCPx and SCP2 are upregulated by the daf-16 like Forkhead transcription factor FOXO3a (also known as FKHRL1) on the level of promoter activity. It was recently described that Forkheads regulate protection against (oxidative) stress both in C.elegans and in mammalian cells. We looked into a role for SCP2 in the cellular defense against oxidative damage and found that a fluorescent fatty acid analogue bound to SCP2 is protected against H₂O₂/Cu²⁺ induced oxidative damage. We propose a model for the way SCP2 could protect fatty acids from peroxidation.

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